title: Human phenotypes associated with GATA-1 mutations.
abstract: GATA-1 is one of the six members of the GATA gene family, a group of related transcription factors discovered in the 1980s. In the past few decades, the crucial role of GATA-1 in normal human hematopoiesis has been delineated. As would be expected, mutations in GATA-1 have subsequently been found to have important clinical significance, and are directly linked to deregulated formation of certain blood cell lineages. This paper reviews the functional consequences of GATA-1 mutations by linking specific errors in the gene, or its downstream protein products, to documented human diseases. These five human diseases are: X-linked thrombocytopenia (XLT), X-linked thrombocytopenia with thalassemia (XLTT), congenital erythropoietic porphyria (CEP), transient myeloproliferative disorder (TMD) and acute megarakaryoblastic leukemia (AMKL) associated with Trisomy 21, and, lastly, a particular subtype of anemia associated with the production of GATA-1s, a shortened, mutant isoform of the wild-type GATA-1. The different phenotypic expressions associated with GATA-1 mutations illustrate the integral function of the transcription factor in overall body homeostasis. Furthermore, these direct genotype-phenotype correlations reinforce the importance of unraveling the human genome, as such connections may lead to important therapeutic or preventive therapies.
authors.affiliation: Department of Orthopaedics and Rehabilitation, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: Wendy A
authors.initials: WA
authors.lastname: Ciovacco
authors.forename: Wendy H
authors.initials: WH
authors.lastname: Raskind
authors.forename: Melissa A
authors.initials: MA
authors.lastname: Kacena
mesh_terms: D019070:Cell Lineage; D004314:Down Syndrome; D050982:GATA1 Transcription Factor / Q000235:genetics*; D005786:Gene Expression Regulation; D005838:Genotype; D006801:Humans; D007947:Leukemia, Megakaryoblastic, Acute / Q000235:genetics; D009154:Mutation; D009196:Myeloproliferative Disorders / Q000235:genetics; D010641:Phenotype; D017092:Porphyria, Erythropoietic / Q000235:genetics; D013921:Thrombocytopenia / Q000235:genetics
chemical_list: D050982:GATA1 Transcription Factor; C494688:GATA1 protein, human